InChI=1S/C21H30O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h5,7,9,14-18,22,24-26H,3-4,6,8,10-11H2,1-2H3/t14-,15-,16-,17-,18+,19-,20-,21-/m0/s1 |
LCOVYWIXMAJCDS-FJWDNACWSA-N |
[H][C@@]12CC[C@](O)([C@@H](O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C |
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Homo sapiens
(NCBI:txid9606)
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Found in
blood plasma
(BTO:0000118).
See:
PubMed
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Bos taurus
(NCBI:txid9913)
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Found in
urine
(BTO:0001419).
See:
PubMed
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mammalian metabolite
Any animal metabolite produced during a metabolic reaction in mammals.
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
hormone
Originally referring to an endogenous compound that is formed in specialized organ or group of cells and carried to another organ or group of cells, in the same organism, upon which it has a specific regulatory function, the term is now commonly used to include non-endogenous, semi-synthetic and fully synthetic analogues of such compounds.
(via steroid hormone )
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View more via ChEBI Ontology
(20S)-11β,17,20,21-tetrahydroxypregna-1,4-dien-3-one
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(11β,20S)-11,17,20,21-tetrahydroxypregna-1,4-dien-3-one
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ChemIDplus
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(20S)-hydroxyprednisolone
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ChEBI
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20(S)-hydroxy prednisolone
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ChEBI
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20β-dihydro-PRED
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SUBMITTER
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20β-hydroxyprednisolone
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ChemIDplus
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prednisolone EP impurity G
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ChEBI
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prednisolone impurity G
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ChemIDplus
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2299-46-9
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CAS Registry Number
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ChemIDplus
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Deventer K, Polet M, Van Gansbeke W, Hooghe F, Van Hoecke H, Van Eenoo P (2021) Investigation of the urinary excretion of prednisolone and metabolites after nasal administration: Relevance to doping control. Drug testing and analysis 13, 1897-1905 [PubMed:34081842] [show Abstract] Glucocorticosteroid use in sport is restricted to non-systemic (nasal/ophtamological/dermatological/intra-articular) use. Systemic use is prohibited because of strong inflammatory suppressing effects. Prednisolone is a GC proven to be very effective in the treatment of nasal congestions and allergic rhinitis and its therapeutic use is allowed. To establish normal urinary concentration ranges for nasally administered prednisolone, an excretion study was performed with Sofrasolone® (nasal-inhaler). Six volunteers were administered a high dose (4.5 mg prednisolone in four gifts over a 9-h period). Samples were analysed using a validated LC-MS/MS method monitoring prednisolone (PRED) and the metabolites prednisone (PREDON), 20β-dihydroprednisolone (20βPRED) and 20α-dihydroprednisolone (20αPRED) in the total fraction (glucuroconjugated and free). Maximum concentrations were 266, 500, 350 and 140 ng/ml for PRED, PREDON, 20βPRED and 20αPRED, respectively. These results show that the current reporting limit of 30 ng/ml in urine can be easily exceeded after therapeutic use. Hence, to avoid false-positive findings related to nasal application, this limit should be increased. To investigate the degree of glucuronidation of PRED and its metabolites also the free fraction was investigated. This shows that PREDON has the highest glucuroconjugation (50%). PRED, 20βPRED and 20αPRED only show less than 20% conjugation. | Van Meulebroek L, De Clercq N, Vanden Bussche J, Devreese M, Fichant E, Delahaut P, Croubels S, Vanhaecke L (2017) Pharmacokinetic and urinary profiling reveals the prednisolone/cortisol ratio as a valid biomarker for prednisolone administration. BMC veterinary research 13, 236 [PubMed:28806969] [show Abstract]
BackgroundIn Europe, synthetic corticosteroids are not allowed in animal breeding for growth-promoting purposes. Nevertheless, a high prevalence of non-compliant urine samples was recently reported for prednisolone, however, without any indication of unauthorized use. Within this context, 20β-dihydroprednisolone and the prednisolone/cortisol ratio have been suggested as potential tools to discriminate between exogenous and endogenous urinary prednisolone. In this study, the validity of these strategies was verified by investigating the plasma pharmacokinetic and urinary excretion profiles of relevant glucocorticoids in bovines, subjected to exogenous prednisolone treatment or tetracosactide hexaacetate administration to induce endogenous prednisolone formation. Bovine urine and plasma samples were analysed by liquid chromatography and mass spectrometry.ResultsBased on the plasma pharmacokinetics and urinary profiles, 20β-dihydroprednisolone was confirmed as the main prednisolone-derived metabolite, being detected in the biological fluids of all 12 bovines (plasma AUC0-inf of 121 h μg L-1 and urinary concentration > 0.695 μg L-1). However, this metabolite enclosed no potential as discriminative marker as no significant concentration differences were observed upon exogenous prednisolone treatment or tetracosactide hexaacetate administration under all experimental conditions. As a second marker tool, the prednisolone/cortisol ratios were assessed along the various treatments, taking into account that endogenous prednisolone formation involves the hypothalamic-pituitary-adrenal axis and is associated with an increased cortisol secretion. Significantly lower ratios were observed in case of endogenous prednisolone formation (i.e. ratios ranging from 0.00379 to 0.129) compared to the exogenous prednisolone treatment (i.e. ratios ranging from 0.0603 to 36.9). On the basis of these findings, a discriminative threshold of 0.260 was proposed, which allowed classification of urine samples according to prednisolone origin with a sensitivity of 94.2% and specificity of 99.0%.ConclusionThe prednisolone/cortisol ratio was affirmed as an expedient strategy to discriminate between endogenous and exogenous prednisolone in urine. Although the suggested threshold value was associated with high specificity and sensitivity, a large-scale study with varying experimental conditions is designated to optimize this value. | Matabosch X, Pozo OJ, Pérez-Mañá C, Papaseit E, Segura J, Ventura R (2015) Detection and characterization of prednisolone metabolites in human urine by LC-MS/MS. Journal of mass spectrometry : JMS 50, 633-642 (Source: SUBMITTER) [PubMed:25800201] [show Abstract] Glucocorticosteroids are prohibited in sports when used by systemic administrations (e.g. oral), whereas they are allowed using other administration ways. Strategies to discriminate between administrations routes have to be developed by doping control laboratories. For this reason, the metabolism of prednisolone (PRED) was studied using liquid chromatography coupled to tandem mass spectrometry. A single oral (10 mg) dose of PRED was administered to two healthy male volunteers. Urine samples were collected up to 6 days after administration. Samples were hydrolyzed with β-glucuronidase and subjected to liquid-liquid extraction with ethyl acetate in alkaline conditions. The extracts were analyzed by liquid chromatography coupled to tandem mass spectrometry. Precursor ion scan methods (m/z 77, 91, 105, 121, 147 and 171) in positive ionization and neutral loss scan methods (76 and 94 Da) in negative ionization modes were applied for the open detection of PRED metabolites. Using these methods, PRED parent compound plus 20 metabolites were detected. PRED and 11 metabolites were characterized by comparison with standards of the compounds (PRED, prednisone, 20β-dihydro-PRED and 20α-dihydro-PRED, 20β-dihydro-prednisone and 20α-dihydro-prednisone, 6β-hydroxy-PRED and 6α-hydroxy-PRED, 20β isomers and 20α isomers of 6β,11β,17α,20,21-pentahydroxypregnan-1,4-diene-3-one, 6α,11β,17α,20β,21-pentahydroxypregnan-1,4-diene-3-one and Δ(6) -PRED). Using mass spectrometric data, feasible structures were proposed for seven of the remaining nine detected metabolites, including several 6-hydroxy-metabolites. Eleven of the characterized metabolites have not been previously described. Maximum excretion rates for PRED metabolites were achieved in first 24 h; however, most of the metabolites were still detectable in the last collected samples (day 6). | Nebbia C, Capra P, Leporati M, Girolami F, Barbarino G, Gatto S, Vincenti M (2014) Profile of the urinary excretion of prednisolone and its metabolites in finishing bulls and cows treated with a therapeutic schedule. BMC veterinary research 10, 237 [PubMed:25267433] [show Abstract]
BackgroundPrednisolone was one of the first glucocorticoids to be synthesised, but it is still widely applied to cattle. Illegal uses of prednisolone include its uses for masking a number of diseases before animal sale and, at lower dosages for extended periods of time, for the improvement of feed efficiency and carcass characteristics. Since occasional presence of prednisolone has been detected at trace level in urine samples from untreated cattle, the Italian Ministry of Health introduced a provisional limit of 5 ng/mL to avoid false non-compliances. However, this limit proved ineffective in disclosing prednisolone misuse as a growth-promoter. In the present study, prednisolone acetate was administered to finishing bulls and cows according to a therapeutic protocol (2 × 0.4-0.5 mg/kg bw i.m. at 48 h interval) to further verify the practical impact of this cut-off limit and develop sound strategies to distinguish between exogenous administration and endogenous production. Urinary prednisolone, prednisone, 20β-dihydroprednisolone, 20α-dihydroprednisolone, 20β-dihydroprednisone, 6β-hydroxyprednisolone, cortisol, and cortisone were determined using a validated LC/MS-MS method.ResultsThe urinary excretion profile showed the simultaneous presence of prednisolone, 20β-dihydroprednisolone, and prednisone, the latter at lower concentrations, up to 33 days after the first dosing. Higher analyte levels were detected in bulls even after correction for dilution in the urine. Prednisolone concentrations below 5 ng/ml were determined in half of the samples collected at 19 days, and in all the samples obtained 26 and 33 days after the first administration. No measurable concentrations of prednisolone or its metabolites were found in the samples collected before the treatment, while cortisol and cortisone levels lower than the respective LOQs were observed upon treatment.ConclusionsThe present study confirms the criticism of the coarse quantitative approach currently adopted to ascertain illegal prednisolone administration in cattle. As previously shown for growth-promoting treatments of meat cattle, the simultaneous determination of urinary prednisolone, prednisone, 20β-dihydroprednisolone, along with cortisol and cortisone, may represent a more reliable approach to confirm the exogenous origin of prednisolone. Such a strategy would facilitate unequivocal detection of animals treated with prednisolone acetate using a therapeutical protocol, even 3 to 4 weeks after the treatment. | Leporati M, Capra P, Cannizzo FT, Biolatti B, Nebbia C, Vincenti M (2013) Determination of prednisolone metabolites in beef cattle. Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment 30, 1044-1054 [PubMed:23510304] [show Abstract] Prednisolone is a synthetic corticosteroid acting on both hydrosaline balance and metabolism that is liable to fraudulent administration to meat-producing animals for growth-promoting purposes. Its use outside strict therapeutic control and prescription is banned by the European legislation, but official controls are hampered by its negligible direct excretion into the urinary matrix. Recent studies reported on a potential endogenous origin of prednisolone in animals subjected to stressful conditions, accounting for its occasional detection in control urines. The objective of the present study was the identification and quantification of prednisolone urinary metabolites to be used as illicit treatment biomarkers in place of the parent drug. An LC-MS/MS screening was conducted on urine samples collected from a bullock intramuscularly administered with prednisolone acetate by using a therapeutic protocol (2 × 0.52 mg kg(-1) at 48-hour interval). Four prednisolone metabolites were identified: 20β-dihydroprednisolone, 20α-dihydroprednisolone, 6β-hydroxyprednisolone and 20β-dihydroprednisone; the first was detected at relatively high concentrations. An existing quantitative LC-MS/MS method was expanded and revalidated to include these metabolites. The new analytical method proved sensitive (LODs: 0.35-0.42 ng mL(-1)) and specific and was applied to urine samples collected from eight beef cattle subjected to low-dosage oral administration of prednisolone acetate for a 35-day period, as in standard growth-promoting treatments. 20β-Dihydroprednisolone was detected in all urine samples collected during the treatment, at relatively high concentration (1.2-27 ng mL(-1)), whereas the prednisolone concentration was virtually negligible (<0.7 ng mL(-1)). 20β-Dihydroprednisolone was no longer present in almost all samples collected 6 days after the end of the treatment, but trace amounts of this metabolite were found in two urine samples from control animals. 20β-Dihydroprednisolone is proposed as an effective biomarker to test illegal growth-promoting treatments with prednisolone in meat cattle, alternatively to the parent drug. | Dodds HM, Taylor PJ, Johnson LP, Mortimer RH, Pond SM, Cannell GR (1997) Cortisol metabolism and its inhibition by glycyrrhetinic acid in the isolated perfused human placental lobule. The Journal of steroid biochemistry and molecular biology 62, 337-343 [PubMed:9408088] [show Abstract] We have previously reported the placental metabolism of prednisolone to prednisone, 20alpha- and beta-dihydroprednisone and 20beta-dihydroprednisolone. In this study, the disposition of cortisol was investigated in vitro in the dual perfused, isolated human placental lobule after the addition of cortisol (1.2 micromol, n = 3 and 12 micromol, n = 4) to the maternal compartment. Analysis of 5 h maternal and fetal perfusate samples by high performance liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS) revealed that cortisol was mainly metabolized to cortisone, but a significant production of 20alpha-dihydrocortisone, 20beta-dihydrocortisone, 20alpha-dihydrocortisol and 20beta-dihydrocortisol was also detected. Saturability of metabolism but not transfer was demonstrated. Metabolism was eliminated by co-perfusion with the potent 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzyme inhibitor 18beta-glycyrrhetinic acid (GA). The disposition of GA was analysed using HPLC-atmospheric pressure chemical ionisation-MS/MS (HPLC-APCI-MS/MS). GA was found to transfer from the maternal to the fetal circulations without detectable metabolism during 6 h of perfusion. | Tembo AV, Ayres JW, Sakmar E, Hallmark MR, Wagner JG (1977) Plasma prednisolone concentrations: comparison of radioimmunoassay and competitive protein binding assay. Steroids 29, 679-693 [PubMed:898234] [show Abstract] A comparison was made between plasma concentrations of prednisolone measured by both competitive protein binding radioassay (CPB) and radioimmunoassay (RIA) and, with each assay, using a calibration curve generated from individual subject data and from pooling the individual calibration curva data. The plasma samples were obtained from six normal adult male volunteers who were pretreated with dexamethasone to suppress endogenous hydrocortisone and who then ingested 10 mg of prednisolone. Both the standard curve data and the plasma concentrations were evaluated statistically. It was shown that the CPB method has considerably greater precision than the RIA method and could be employed in bioavailability and pharmacokinetic studies of both prednisolone and prednisone. It was also shown that corticosteroid binding globulin cross-reacts considerably less with the major metabolite of prednisolone, 20beta-dihydroprednisolone, than the particular antiserum used in the RIA. |
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